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Inhibition of the cancer target human hyaluronidase Hyal‑1 by natural substances
* 1 , 1 , 2 , 3 , 4 , 1
1  Institute of Pharmaceutical and Medicinal Chemistry, Pharma Campus, Westfälische Wilhelms-Universität, Corrensstraße 48, 48149 Münster, Germany
2  Institute of Pharmacy, Freie Universität Berlin, Königin Luise Str. 2+4, 14195 Berlin, Germany
3  Department of Pharmaceutical/Medicinal Chemistry II, Institute of Pharmacy, University of Regensburg, Universitätsstr. 31, 93040 Regensburg, Germany
4  Institute of Pharmaceutical Biology and Phytochemistry, PharmaCampus, Westfälische Wilhelms-Universität, Corrensstraße 48, 48149 Münster, Germany

Published: 02 November 2015 by MDPI in 1st International Electronic Conference on Medicinal Chemistry session ECMC-1

The negatively charged polysaccharide Hyaluronic acid (HA) has diverse physiological and pathophysiological functions depending on its chain size. Space‑filling, anti‑inflammatory and antiangiogenic effects are triggered by high molecular weight HA (HMW HA) (>20 kDa). Hydrolyzation of HMW HA by Hyal‑1 results in low molecular weight HA (LMW HA) (<20 kDa) which leads to inflammatory and angiogenic effects.[1] For this reason Hyal‑1 is an interesting target for drug discovery. The surface display of active Hyal‑1 on Escherichia coli, via Autodisplay, enables the screening for potential inhibitors in a whole cell system. Based on this technique we determined the inhibitory effect of different natural substances on human Hyal-1. The IC50 values of the plant extracts Malvae sylvestris flos, Equiseti herba and Ononidis radix were determined to be between 1.4 and 1.7 mg/mL. Furthermore, the IC50 values of four triterpenoid saponines were determined. The obtained IC50 value for glycyrrhizinic acid, a known Hyal-1 inhibitor, was 177 µM. The IC50 values for the newly identified inhibitors gypsophila saponin 2, SA1641, and SA1657 were 108 µM, 296 µM and 371 µM, respectively.[2] For the synthesis of new small molecule inhibitors targeting human Hyal-1 these extracts and natural compounds could be used as a starting point.


[1]   Stern R, Semin Cancer Biol, 2008, 18, 275-280.

[2]   Orlando Z, et al. Molecules, 2015, 20, 15449-15498.

Keywords: Hyaluronidase, Hyaluronic acid, cancer, natural compounds